Elsevier

Journal of Hepatology

Volume 48, Issue 1, January 2008, Pages 140-147
Journal of Hepatology

Impact of gender on the long-term outcome and survival of patients with autoimmune hepatitis

https://doi.org/10.1016/j.jhep.2007.08.013Get rights and content

Background/Aims

Autoimmune hepatitis (AIH) predominantly affects women. Reasons for this are unclear and few series have assessed long-term outcomes of men with AIH.

Methods

To evaluate the clinical course and outcomes of 51 men from a total of 238 consecutive patients with definite AIH at a single centre from 1971 to 2005. The primary outcome measure was death or liver transplantation.

Results

Median age at diagnosis was 39 y in men and 49 y in women (p = 0.0589). HLA A1, B8 and DR3 allotypes and the HLA A1–B8–DR3 haplotype were more frequently expressed in men (63% vs. 45%, p = 0.049; 74% vs. 38%, p < 0.001; 62% vs. 44%, p = 0.058; and 50% vs. 23%, p = 0.003; respectively). There were no significant differences in clinical manifestations at presentation. Over 96% of patients demonstrated a complete initial response to treatment. A greater number of men experienced at least one relapse (71% vs. 55%, p = 0.0591). However, women were significantly more likely to die or require liver transplantation (Log rank test p = 0.024).

Conclusions

Men with AIH appear to have a higher relapse rate and younger age of disease onset which may relate to increased prevalence of HLA A1–B8–DR3. Despite this, men have significantly better long-term survival and outcomes than women.

Introduction

Autoimmune hepatitis (AIH) is a disease of the hepatic parenchyma characterised by progressive inflammatory destruction. It is associated with a female preponderance, the presence of circulating autoantibodies, hypergammaglobulinaemia, interface hepatitis on liver biopsy, and it typically responds to immunosuppressive therapy [1].

The observed female gender bias is consistent with many other autoimmune diseases where there is likewise an increased susceptibility in women. Although the reasons behind this are unclear, it is well established that hormones and the hypothalamic–pituitary–gonadal system may modulate the immune response [2], [3], [4], [5], [6], [7], [8], [9], [10]. Physiological examples include amelioration of disease activity during pregnancy in patients with multiple sclerosis (MS) and rheumatoid arthritis (RA) [9], [10]. In patients with AIH, amelioration of disease activity from the second trimester of pregnancy, followed by post-partum flares, has been demonstrated in two series [11], [12]. In one of these series, disease exacerbation during pregnancy was also demonstrated, albeit in only 4/35 (11.4%) pregnancies [12].

Given the alteration of disease behaviour in conditions such as MS and RA under different hormonal environments, it might also be expected that disease expression and clinical outcome differ according to gender. Indeed, male patients with MS demonstrate more severe disease with an increased rate of cerebellar involvement, higher rates of primary progressive disease and require assisted walking devices after a shorter time period than women [13]. Conversely in RA, disease activity is more severe and long-term outcome poorer in female patients although male patients are more likely to die from extra articular manifestations of the disease [14].

To date, there has been little described pertaining to the influence of gender on the course and outcome of AIH. A report by Czaja et al. [15] investigated outcomes in a large US tertiary referral centre and found no differences in clinical outcome between 144 women and 41 men with AIH, although an increased frequency of concurrent autoimmune diseases and an increased prevalence of human leucocyte antigen (HLA) DR4 in female patients compared to male patients were noted [15].

In view of the paucity of existing data regarding the influence of gender on patients with definite AIH, we have investigated factors affecting susceptibility to the disease, presentation, severity of illness and outcome between men and women who fulfilled diagnostic criteria for definite AIH in a European setting.

Section snippets

Methods

The medical records of 238 patients (51 male, 187 female) with a diagnosis of definite AIH, median International AIH Group (IAIHG) [1], [16] score 22 (range 16–28), who presented between 1971 and 2005 at King’s College Hospital (KCH) were examined from a prospectively obtained database. The influence of gender on presentation, clinical course, response to therapy, incidence of hepatocellular carcinoma and clinical outcome (time to either death or liver transplantation (LT)) was evaluated.

Patient demographics and laboratory parameters at presentation

The female to male ratio was approximately 4:1 in our patient cohort. Both groups of patients were followed for a similar length of time (median 14 years, range 1–35 y for males vs. 11 y, range 0.1–30 y for females, p = 0.0773) (Table 1). Female patients tended to be older at presentation (median age 39 y for males vs. 49 y for females, p = 0.0589). The age distribution for men and women is illustrated in Fig. 1. There were no statistically significant differences between the two groups with regard to

Discussion

This large, single, tertiary centre study provided the opportunity to undertake a comprehensive analysis of the influence of gender on outcomes and disease severity in AIH. The most striking difference demonstrated in this study was that men with AIH appeared to have better long-term survival and outcome than their female counterparts. Furthermore, expression of HLA A1, B8, DR3 allotypes and the HLA A1–B8–DR3 haplotype was all increased in male patients compared to female patients. Men with AIH

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    The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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